A Neurally Mediated Inotropic Effect of Veratridine and Cevadine on Isolated Guinea-pig Papillary Muscle

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1980 Nov 1

PMID 6256668

Authors

P Honerjager

Affiliations

Soon will be listed here.

Abstract

The positive inotropic effect of veratridine and cevadine was investigated in the isolated, isometrically contracting guinea-pig papillary muscle. The increase of the force of the rested-state contraction, elicited after incubation of the resting muscle with veratridine or cevadine, served as a measure of the neurally mediated, sympathomimetic effect of these alkaloids. Concentrations exceeding 5 mumol/l veratridine or 15 mumol/l cevadine produced concentration-dependent increases of the force of the rested-state contraction. These concentrations are larger than those causing the maximum positive inotropic effect on muscles contracting continually at a rate of 1 Hz. The positive inotropic effect of 30 mumol/l veratridine as manifested by the rested-state contraction was absent in the presence of 100 nmol/l tetrodotoxin and in muscles from reserpine-pretreated animals. It was significantly inhibited by 50 nmol/l (-)-propranolol, but not by the same concentration of (+)-propranolol. The effect of 30 or 60 mumol/l cevadine was likewise absent in catecholamine-depleted preparations. It is concluded that the indirect inotropic effect of veratridine or cevadine, which is attributed to their noradrenaline-releasing effect on intracardiac nerves, requires higher concentrations than the direct positive inotropic effect, which is a consequence of the increased transsarcolemmal influx of Na ions into the myocardial cell.

References

Feinstein M, Paimre M . Mechanism of cardiovascular action of tetrodotoxin in the cat. Block of conduction in peripheral sympathetic fibers. Circ Res. 1968; 23(4):553-65. DOI: 10.1161/01.res.23.4.553. View

Honerjager P, Reiter M . The cardiotoxic effect of batrachotoxin. Naunyn Schmiedebergs Arch Pharmacol. 1977; 299(3):239-52. DOI: 10.1007/BF00500316. View

Baer M, Best P, Reuter H . Voltage-dependent action of tetrodotoxin in mammalian cardiac muscle. Nature. 1976; 263(5575):344-5. DOI: 10.1038/263344a0. View

Honerjager P, Reiter M . The relation between the effects of veratridine on action potential and contraction in mammalian ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1975; 289(1):1-28. DOI: 10.1007/BF00498026. View

Shotzberger G, Albuquerque E, Daly J . The effects of batrachotoxin on cat papillary muscle. J Pharmacol Exp Ther. 1976; 196(2):433-44. View

Shibata S, NORTON T, Izumi T, Matsuo T, Katsuki S . A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. J Pharmacol Exp Ther. 1976; 199(2):298-309. View

Honerjager P . Electrophysiological effects of various ceveratrum alkaloids on single nerve axons. Naunyn Schmiedebergs Arch Pharmacol. 1973; 280(4):391-416. DOI: 10.1007/BF00506631. View

Ross S, Kelder D . Release of 3H-noradrenaline from the rat vas deferens under various in vitro conditions. Acta Physiol Scand. 1979; 105(3):338-49. DOI: 10.1111/j.1748-1716.1979.tb06349.x. View

Thoa N, Wooten G, Axelrod J, Kopin I . On the mechanism of release of norepinephrine from sympathetic nerves induced by depolarizing agents and sympathomimetic drugs. Mol Pharmacol. 1975; 11(1):10-8. View

10.

Romey G, Renaud J, Fosset M, Lazdunski M . Pharmacological properties of the interaction of a sea anemone polypeptide toxin with cardiac cells in culture. J Pharmacol Exp Ther. 1980; 213(3):607-15. View

11.

Fujiwara M, Muramatsu I, Hidaka H, Ikushima S, Ashida K . Effects of Goniopora toxin, a polypeptide isolated from coral, on electromechanical properties of rabbit myocardium. J Pharmacol Exp Ther. 1979; 210(2):153-7. View

12.

CORABOEUF E, Deroubaix E . Effect of toxin II isolated from scorpion venom on action potential and contraction of mammalian heart. J Mol Cell Cardiol. 1975; 7(9):643-53. DOI: 10.1016/0022-2828(75)90141-8. View

13.

Horackova M, Vassort G . Excitation--contraction coupling in frog heart. Effect of veratrine. Pflugers Arch. 1974; 352(4):291-302. DOI: 10.1007/BF00585683. View

14.

Honerjager P, Reiter M . Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine. Circ Res. 1977; 40(1):90-8. DOI: 10.1161/01.res.40.1.90. View

15.

Reiter M . [Evaluation of inotropically active drugs on isolated papillary muscle]. Arzneimittelforschung. 1967; 17(10):1249-53. View

16.

Moss J, Thoa N, Kopin I . On the mechanism of scorpion toxin-induced release of norepinephrine from peripheral adrenergic neurons. J Pharmacol Exp Ther. 1974; 190(1):39-48. View

17.

Howe R, Shanks R . Optical isomers of propranolol. Nature. 1966; 210(5043):1336-8. DOI: 10.1038/2101336a0. View

18.

ULBRICHT W . The effect of veratridine on excitable membranes of nerve and muscle. Ergeb Physiol. 1969; 61:18-71. DOI: 10.1007/BFb0111446. View

19.

Akera T, Ku D, Frank M, BRODY T, Iwasa J . Effects of grayanotoxin I on cardiac Na + K + -adenosine triphosphatase activity, transmembrane potential and myocardial contractile force. J Pharmacol Exp Ther. 1976; 199(1):247-54. View

20.

Horackova M, Vassort G . Ionic mechanism of inotropic effect of veratrine on frog heart. Pflugers Arch. 1973; 341(4):281-4. DOI: 10.1007/BF01023669. View